Finding Lifesaving Solutions to a Dangerous Trend

How one ASAM member’s interest in the latest street drug xylazine went viral. 

Kelly S. Ramsey, MD, MPH, MA, DFASAM, didn’t set out to be a so-called “expert” on the drug xylazine.  

After seeing an increase in xylazine’s prevalence in the illicit drug supply and noticing a lack of information about it in mainstream media, Dr. Ramsey did a deep dive into the literature on the substance. When she participated in a webinar on the topic earlier this year and the video went viral on YouTube, she had no choice but to continue talking about the life-threatening trend.  

“I’ve been interviewed frequently about xylazine by press around the country, and I’ve been asked by a variety of ASAM chapters to speak about xylazine,” said Dr. Ramsey, President for the NYSAM Board of Directors and Chief of Medical Services for OASAS: Office of Addiction Services and Supports in Albany, New York. “It just sort of happened.”  

The Problem 

Known on the street as “tranq,” “tranq dope,” and “anestesia de caballo,” xylazine has been used as a sedative for large animals, such as horses and cows, for decades. In the 1960s, it was briefly considered for use in humans, but, due to side effects that include profound central nervous system sedation, it never received approval.  

“Essentially, it makes people unconscious,” Dr. Ramsey said. 

In the 1980s and 1990s, cases of xylazine’s misuse among humans were occasionally reported. Misuse grew in Puerto Rico in the early 2000s. Then, in 2006, human use of the tranquilizer dramatically increased in Philadelphia, Pennsylvania. By 2021, an alarming statistic emerged from the city. 

“Ninety percent of the syringes that had fentanyl in them, also contained xylazine,” Dr. Ramsey said.  

Today, the trend of xylazine used with fentanyl is seen throughout the United States. Dr. Ramsey said that recent data from DEA seizures shows that xylazine has been confiscated in the fentanyl supply in all but two states.  

“When it's being mixed in with fentanyl, we suspect it's to extend the duration of the effect of fentanyl on the individual person who's using,” Dr. Ramsey said. “Fentanyl is actually a short duration of action substance, so when you add xylazine to it, it potentiates the duration of the fentanyl effects.” 

When combined with fentanyl, xylazine’s effect on users is unpredictable, depending on the amount of it added to the mix. 

“It causes sedation for a long period of time,” she said. “The average is probably about four hours, but again, depending on the amount that's in the substance, it could be as long as eight to 10 hours.” 

Of course, there are numerous consequences to consider when someone is unconscious for such a long time. Potential medical complications include rhabdomyolysis, a deep vein thrombosis, or a blood clot.  

“You also have to think about the vulnerability of those affected by xylazine to things like sexual assault, physical assault, robbery, etc.,” Dr. Ramsey added. “There are many potential consequences.” 

Treating the Problem 

When treating patients who’ve overdosed on the mixture of xylazine with fentanyl, Dr. Ramsey advises the use of naloxone. However, in a polysubstance overdose with substances that are non-opioids, naloxone alone may not provide a successful reversal.  

“You should give a dose of naloxone, activate EMSs, wait two full minutes for that naloxone dose to have effect, and then if it does not have the expected effect, give a second dose of naloxone,” she said. “Our goal when giving naloxone should be to approximate normalization of breathing. If you do not get that response after two doses of naloxone, you need to pivot and think about polysubstance overdose, which could include xylazine, designer drugs, benzodiazepines, and many other substances that would not be responsive to naloxone because they're not opioids.” 

Because xylazine is a muscle relaxant, it’s important to support the patient’s breathing and consider that the relaxed tongue could block their airway.  

“If you don't do other maneuvers to support breathing, and you're only relying on naloxone, you may not be successful,” Dr. Ramsey said.  

One often-reported side effect of xylazine is the creation of wounds, which, if left untreated, can progress to large ulcerated, open wounds.  

“If they progress to that state, often times the individual doesn't want to seek care because they've either been stigmatized when they seek care, or they're ashamed of what the wound looks like,” Dr. Ramsey said. “It's crucial for medical providers to recognize the wounds early and understand how to intervene to prevent them from becoming more complex.” 

When discussing xylazine-related wounds, Dr. Ramsey said it’s important to not foster drug panic with inflammatory language such as “flesh-eating” and “zombie drugs,” which occasionally are used in the media. 

“All that language does is alienate people, and it also increases stigma toward people who may be intentionally using that substance, or even unintentionally using that substance,” she said. “When we create fear around a substance, we also create myths around a substance. We've seen this, especially with respect to fentanyl.” 

Dr. Ramsey said the pathophysiological mechanism by which xylazine leads to skin wounds in individuals is unknown at this point. A wound can form at the site of injection, but wounds can also occur at a site where injections do not occur. Those who sniff xylazine or insert it rectally can develop wounds elsewhere.  

“You can see a wound just from xylazine use,” she said. “I think it's important when we're engaging with people who use drugs, and particularly for medical providers in emergency department/ urgent care settings where they may see somebody for another reason, but they have a skin wound – it's important to talk to people about what they're using. 

“If someone is using fentanyl, it's likely that, depending on where you are, they may also be exposed to xylazine, unintentionally or intentionally” 

Getting Involved 

Dr. Ramsey traces her interest in addiction medicine to her experience in harm reduction. While working in a community health center in Santa Cruz, California, in the 1990s, she became interested in HIV and Hepatitis C and volunteered at the Santa Cruz Needle Exchange. The more she talked with patients and got to hear their stories, the more she realized addiction can happen to anyone.  

“I saw the thread of trauma through most of the individuals’ lives and felt like everything that I had ever been told growing up in suburban New Jersey about substance use was a lie,” she said.  

Dr. Ramsey entered medical school intending to treat people who use drugs and, today, she’s thankful she did.  “I find it extraordinarily rewarding to treat people who use drugs,” she said. 

Dr. Ramsey joined ASAM in the early 2000s, shortly after completing her residency. She has since attended numerous ASAM Annual Conferences. Five years ago, she joined her state chapter of ASAM, NYSAM, through which she has served as chair of the education committee and president-elect. Currently, she is the Region 1 Director and President of NYSAM and serves on the Board of Directors for both ASAM and NYSAM.  

Recently, Dr. Ramsey contributed to the recently published, ASAM Clinical Considerations: Buprenorphine Treatment of Opioid Use Disorder (OUD) for Individuals Using High-Potency Synthetic Opioids (HPSOs). The document was published online in late July by the Journal of Addiction Medicine. It includes six pressing clinical questions related to the topic – the responses to which Ramsey helped write.  

“The question that I most specifically worked on was, ‘How do adulterants in the drug supply, like xylazine and others, impact initiation of buprenorphine?’” she said. “I used xylazine as an example and talked about some of the issues and things for clinicians to consider.” 

Dr. Ramsey said she believes the document could be helpful for physicians. 

“I think it's an important reference point, because if someone is already a buprenorphine prescriber, then, depending on where they are geographically, they're probably already seeing some complications when using a traditional initiation method with their patients,” she added. “This is a great resource to help address some of those challenges they may be seeing or may see in clinical practice.” 

While she’s contributed to numerous NYSAM projects, Dr. Ramsey said her work on this Clinical Considerations document was her first experience participating on an ASAM-specific project. 

“It really prompted me to become more involved with ASAM through committee work; I'm going to be part of a team looking at ASAM’s bylaws and charter,” she said. “I also look forward to participating on the Annual Conference Planning Committee. I'm really excited to be more involved in various ways.” 

Find Your Role 

Dr. Ramsey said she encourages ASAM members to get involved in their state chapters, if they aren’t already. Doing so, she added, can establish a stronger sense of connection, which is important when there’s so much stigma attached to substance use disorder and even the treatment of it. 

“If you're operating in a bubble by yourself and not connecting with colleagues who are like-minded, you could feel isolated in your work,” she said. “I think it's helpful to connect with colleagues and also to encourage younger folks and trainees in the field to get involved in their chapters so they can benefit from the experience of being around others in addiction medicine, addiction psychiatry, etc., and work with them as mentors and help them see the real beauty in doing this work.” 

Part of that beauty, Dr. Ramsey feels, is reliance on community. Although she said the field of addiction medicine, specifically, is critical to combating today’s opioid epidemic and the rise of unregulated substances like xylazine, she also said everyone is needed in the fight. 

“As a society at large, we all have a role in addressing the overdose epidemic and the substance use epidemic,” she said. “Substance use affects almost every family in the United States. We need to stop thinking about it as not affecting us individually, but recognize that it affects our families, our neighbors, our communities, wherever we are, and that the only way that we're going to move to the other side of this is by decreasing stigma, increasing empathy, and recognizing that we all have an active role to play.”